FACTORS INFLUENCING NEONATAL THYROID-STIMULATING HORMONE LEVEL IN NAKHON PATHOM PROVINCE, THAILAND

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1 P-MS057 FACTORS INFLUENCING NEONATAL THYROID-STIMULATING HORMONE LEVEL IN NAKHON PATHOM PROVINCE, THAILAND Samart Punpetch 1, *, Kitipong Hancharean 2, # 1 Master of Science Program in Public Health (Infectious Diseases and Epidemiology), Faculty of Public Health, Mahidol University, Thailand 2 Department of Epidemiology, Faculty of Public Health Mahidol University * samart4epmu@gmail.com, # phkhc@mahidol.ac.th Abstract Background: Thyroid-stimulating hormone in circulation is particularly important for pregnant women to have the correct amounts of thyroid stimulating hormone and neonatal TSH levels must be regulated in order to ensure the healthy development of their babies, especially the central nervous system and brain. (1,3), which hormone is one of the hormones measured in newborns. The World Health Organization (WHO) has suggested that when a sensitive assay is used on samples collected 3 4 days after birth, a <3% frequency of TSH concentrations >5 miu/l (11.2 miu/l in serum) indicates iodine sufficiency in a population. 4-5 However, many studies have attempted to address influencing factors of newborn TSH measurements in determining population iodine status and monitoring intervention programs, and although some have proven to be successful but, most have provided conflicting or uncertain data. This study was designed to investigate factors that influencing neonatal TSH levels. Methods: A case-controls study (1:4) was used to analyze data from questionnaires. Results: Univariate analysis identified variables influencing the high neonatal TSH levels (>11.2 µiu/l). Family income, gestational age at first visit of antenatal care, and iodine tablet supplementation are association with the high neonatal TSH levels. Multivariate analysis identified a number of variables that are independently associated with high neonatal TSH levels (>11.2 µiu/l). Pregnant women who not receive a prenatal iodine tablets supplementation was an increased risk of neonatal TSH levels above 11.2 µiu/l more than who receive a prenatal iodine tablets supplementation (adjusted odds ratio = 7.41 (95% confidence interval = 3.33 to 16.53). Conclusions: In this study, neonate who has high TSH levels (>11.2 µiu/l) did not vary by maternal education, history of abortion, alcohol drink during pregnancy, number of visit for antenatal care, mode of delivery, preterm birth and birth weight of the neonate but was associated with prenatal iodine tablets supplementation and other risk factors, including family income, gestational age at the first antenatal care, and sex of the neonate Keywords: thyroid-stimulating hormone, prenatal supplementation, iodine, neonatal screening Introduction Thyroid stimulating hormone (TSH) is produced by the pituitary gland.its role is to regulate the production of hormones by the thyroid gland. Thyroid hormones such as thyroxine (T4)and triiodothyronine (T3), are importance roles in the early normal growth and development stages of most human organs, especially the central nervous system and brain. 1 Consequently, thyroid hormone is particularly important for pregnant women to have the correct amounts of thyroid stimulating hormone and thyroid hormones to ensure the healthy development of their babies. 2 Thyroid stimulating hormone is one of the hormones measured in newborns.a simple blood test can measure TSH in the circulation of the neonate, who has too much concentration may indicate that their thyroid gland is not making enough thyroid hormone or iodine deficiency.an adequate iodine intake in the mother is essential for the normal synthesis of maternal and fetal thyroid 1213

2 hormones important for fetal brain development. Insufficient iodine supply from the mother can result in a decreased synthesis of both T4 and T3, with an increased concentration of TSH in the newborn. 1,3 The World Health Organization (WHO) has suggested that when a sensitive assay is used on Neonatal TSH samples collected 3 4 days after birth, a <3% frequency of TSH concentrations >5 miu/l (dried cord blood spot sample collected at delivery) 4-5 or 11.2 mu/l(cord blood serum collected at delivery) indicates iodine sufficiency in a population. A frequency of % indicates mild iodine deficiency and frequencies of % and above 40.0% indicate moderateto severe iodine deficiency, respectively. 6 However, many studies have attempted to apply the frequency of neonatal TSH values >5 miu/l in determining population iodine status and monitoring intervention programs, and although some have proven to be successful but, most have provided conflicting or uncertain data. Neonatal TSH is a sensitive indicator of an inadequate supply of thyroid hormone to the developing brain. This principle underpins the application of newborn TSH screening as anindicator of maternal and hence population iodine nutrition. Thus, neonatal TSH screening may bea powerful and underused tool in monitoring iodine nutrition in mothers and babies. 4-5 However,multiple factors other than maternal iodine status can an influence measurement of newborn TSH, including the timing of the heel-prick collection, maternal or newborn exposure toiodine-containing antiseptics, the collection paper employed for the bloodspot and the TSHassay methodology. 2 Furthermore, many studies have explored the impact of maternal, fetal, and delivery characteristics on neonatal thyroid hormonesstatusinclude mode of delivery, birth order, maternal age, gestational diabetes, alcohol use during pregnancy and the sexof the neonateare independently associated with thyroid hormone levels. 7 To improve understanding derived from past studies, weconducted multivariate analyses to simultaneously examinethe association between neonatal TSH level measures and many factors such as maternal factors, delivery factors, and infant factors that affects the high neonatal TSH level (>11.2 mu/l).the result of this study will be useful for improving in the context of the maternal and child health care and in the context of neonatal TSH screening for monitoring iodine status in Thailand. The Neonatal Screening Program as nationwide screening due to the high incidence of congenital hypothyroidism, especially in iodine deficient areas of the country. In 2005, this program became mandatory and the screening service was provided to all newborns in all hospitals in Thailand.This screening result during showed all provinces of Thailand had sufferred with iodine deficiency and the severity levels of iodine deficiency disorders (IDD) in area were mild IDD (%IDD ) to low IDD (%IDD ). 8 The surveillance and evaluation system of the prevention and control of IDD in Region 4found that the degree of severity was mild IDD to low IDD in area; there are the percentages of IDD as 16.00, 18.48, 16.23, 13.47, and 9.80, respectively. 9 Nakhon Pathom provincewas the mild IDD to low IDD area during , which is not the highest problem of a country, but when compared prevalence of iodine deficiency of a country found that is more prevalence than the country annually.consequently, this study investigated the factors such as maternal factors, delivery factors, and infant factorsinfluencing neonatal TSH in Nakhon Pathom province, Thailand Methodology This study is a case-controls study, matched case and control 1:4.We study in Nakhon Pathom province of Thailand; the study sitesinclude Sampran district, Nakhonchaisri district and Banglen district were selected bypurposive sampling.the Study populations were Thai pregnant women with deliver atsampran hospital, Nakhonchaisri hospital and Banglen hospital since 2011to 2012, and who live in three districts of Nakhon Pathom provinceless than a year. The study population had neonatal TSH screening report and linkage name and address of pregnant women by medical record, and met the following criteria. 1214

3 Inclusion criteria 1. Pregnant women who lives in Sampran district, Nakhon Pathom province during pregnancy, and early pregnancy for at least one year. 2. Neonates of Pregnant women who will have report of neonatal TSH levels under the national neonatal screening program during in 2012 from Sampran hospital. 3. Pregnant women who will consent to participate in the interview by using questionnaires. Exclusion criteria 1. Participants will have loss of data include the maternal iodine intake from iodine tablets use, dietary of seafood and iodized seasoning during pregnancy. The study populations were divided into two groups by the criteria of cases and controls group, which have the following definition; Casewas pregnant women who have neonates with neonatal TSH levels in the serum at 48 hours of life are greater than 11.2 mu / l. Controlwas pregnant women who have neonates with neonatal TSH levels in the serum at 48 hours of life are less than or equal to11.22 mu / l. The estimate of sample size of study is 350 which divide into 70 cases and 110 controls; this paper presented only 60% (51cases and 198 controls)of sample of study. The study population was confirmed the cases and controls by neonatal TSH level.the sampling frame was listedof the name of participants, 220 samples will be drawn by random from all pregnant women. We were collected data by questionnaire,which include characteristics of mother, iodine tablets use during pregnancy, consumption of seafood and others food that containing iodineconsumption of iodized salt and others iodized seasoning product, and characteristics of the neonate. All data from questionnaireswas checked for accuracy and entered into the computer file for the analysis.after the completeness of data will find the accuracy and the researchers develop the coding for recording data. The data analysis using SPSS software, the statistical analysis as carried out as follows; 1. Descriptive statistics: frequency, percentage, means and standard deviation. It can be used to describe the samples. 2. The analytic statistic: The following statistic was used; 2.1 Univariate analysis will carry out to study the association with the single exposure variable and neonatal iodine deficiency using chi-square test and logistic regression technique. 2.2 Multivariate analysis will carry out to study the association with many exposure variables and neonatal iodine deficiency, controlling the confounding effect of each variable using multiple logistic regression technique. Results Table 1 presents the distribution (numbers and column percentage) of cases and controls groups by maternal factor, neonate factor and delivery factors. Maternal factors Maternal age at pregnancy, most of participants of cases and controls were years 49 % and 31.1%, respectively. (P-value=0.006) Education, most of participant of cases and controls had the education at high school 56.8% and 66.7%, respectively. Family income, most of cases had the family income > 15,000 bath 41% and controls had the family income < 10,000 bath. (p value =0.006) 1215

4 History of abortion, most cases and controls did not have the history of abortion 88.2% and 92.9%, respectively. Alcohol drink during pregnancy, most of cases and controls did not drink alcohol (90.2%, 96%) Gestational age at the first visit for antenatal care, most of case and control had>12 weeks of gestational age at the first visit for antenatal care 58.8% and 73.7%, respectively.(p-value =0.037) Number of visit for antenatal care, most of cases and controls had number of visit for ANC <5 times 76.5%, 73.7%, respectively. Iodine tablet supplementation, most of cases did not took the iodine tablet supplement 56.9% and controls group had took the iodine table supplement 84.8 (p value<0.001) Neonate factor Birth Order of the neonate, most of cases had the 1st of birth order 70.6% and controls had the other or more than 164.1%, respectively. (P-value <0.001) Sex of neonate, most of case was male 62.7% and control was female 56.1 %.( p value=0.017) Preterm birth, most of cases and controls did not Preterm birth 86.3% and89.9%, respectively. Birth weight, most of cases and controls had birth weight of baby between 2,500-2,999 gram 47.1% and 51.5%, respectively. Delivery Factor Mode of delivery, most of cases and controls had vaginal delivery 88.4% and 85.4%, respectively. Table 2 presents the distribution Odds ratio with 95% confidence intervals by using univariate analyses. High levels of neonatal TSH at delivery (>11.2 miu/l) were not associated with maternal age (modeled both continuously and categorically) and birth order of the neonate. Family income, the pregnancy who had the family income <10,000, 10,000-15,499 bath had the risk to high levels of neonatal TSH two-tree times of pregnancy who had family income > 15,000 bath (OR=2.721, CI= ), (OR=3.084, CI= ), respectively. Gestational age at the first visit for antenatal care, The pregnancy who had the Gestational age at the first visit for antenatal care<12 weeks had the risk to high levels of neonatal TSH two times of the pregnancy who had Gestational age at the first visit for antenatal care > 12 weeks. (OR=1.97, CI= ). Iodine tablet supplementation, the pregnancy who had did not took the iodine tablet supplement had the risk to high levels of neonatal TSHseven times of the pregnancy who had took the iodine tablet.(or= 7.382, CI= ). In addition, Sex of neonate, the pregnancy who had female neonate had the risk to high levels of neonatal TSHtwo times of pregnancy who had male neonate. (OR= 2.149, CI = ). 1216

5 Table 1. Number and percentage of cases and control by variable Characteristics case controls n % n % Age at pregnancy Education < high school high school >high school Family income <10, Birth order of the neonate 10,000-15, , th other History of abortion yes no Alcohol drink yes no Gestational age at the 12 weeks first visit for antenatal care <12 weeks Number of visit <5 times for ANC 5 times Iodine tablet no supplementation yes Sex of neonate female male Mode of delivery vaginal delivery caesarean section Premature yes no Birth weight <2,500 g ,500-2,999 g ,000-3,499 g ,500 g P-value < <

6 Table2. Odds ratio with 95% confidence intervals variable Odds ratio 95%CI Age at pregnancy Family income <10, ,000-15, , Birth order of neonatepregnancy 1 th Other Gestational age at the first visit for 12 Weeks antenatal care <12 Weeks Iodine tablet supplementation No Yes Sex of neonate Female Male Table3. Odds ratio (adj.) with 95% confidence intervals variable Odds ratio (adj.) 95%CI Age at pregnancy Family income <10, ,000-15, , Birth order of neonate 1 th Other Gestational age at the first visit for 12 Weeks antenatal care <12 Weeks Iodine tablet supplementation No Yes Sex of neonate Female Male The results of the multivariate models are shown in Table 3, presents the distribution Odds ratio adj. with 95% confidence intervals by using multivariate analyses to simultaneously examine the association between high levels of neonatal TSH measures and many factors such as maternal factors, delivery factors, and infant factors. When adjust age at pregnancy, family income, birth order of neonate, gestational age at the first visit for antenatal care, and sex of neonate found that the pregnancy who did not take iodine tablet supplementation had the risk to high levels of 1218

7 neonatal TSHseven times of pregnancy who take the iodine tablet supplementation (adjust OR= 7.41, 95% CI: ). Discussion and Conclusion In Thailand, Iodine Deficiency Disorders (IDD) have been recognized as a serious public health problem for over 50 years. 10 Until recently, immediate measures on prevention of iodine deficiency during pregnancy by iodine tablets supplementation; all pregnant women must obtained iodine tablets at the time of their first visit to antenatal clinics of the government and private health facilities since 1 st October 2010 onwards, which received during pregnancy and continuing while breastfeeding. Maternal behavioral factors including nutrition may also impact thyroid function. Iodine intake is among the most important nutritional factors influencing thyroid hormone level, as it is required for thyroid hormone synthesis, 11 when dietary iodine is insufficient, compensatory mechanisms enable the thyroid gland to hoard more of the available iodine and more efficiently reuse iodide that is released when T4 is converted to T3. 12 During pregnancy, iodine availability is especially important due to the increased demand placed on the maternal thyroid system. It has been shown that maternal iodine deficiency is related to higher TSH concentrations in the newborn, such that, at a population level, the cumulative TSH shifts to the right as the severity of iodine deficiency increases. Many studies have explored the impact of maternal iodine supplementation on thyroid hormones and TSH at birth, mostly in the context of public health programs to provide iodine supplementation. The result of this study was The use of iodine tablet during pregnancy in the prevention of iodine deficiency isthe solution adopted by normal TSH concentrations level, which concordantly the Rebagliato M. study 13 found that there was an increased risk of TSH above 3 µu/l in women who consumed 200 µg or more of iodine supplements daily compared with those who consumed less than 100 µg/day (adjusted odds ratio = 2.5 (95% confidence interval = 1.2 to 5.4)) andrajatanavin R. study 14 found that a low concentration of iodine in the urine of a rural mother was associated with a five-fold greater chance of her neonate having a serum TSH concentration higher than neonates born in Bangkok, concordantly this studythe use of iodine tablet during pregnancy in the prevention of iodine deficiency is the solution adopted by normal TSH concentrations level. References 1. Delange F. The disorders induced by iodine deficiency. Thyroid 1994;4(1): Travers CA, Guttikonda K, Norton CA, Lewis PR, Mollart LJ, Wiley V, et al. Iodine status in pregnant women and their newborns:are our babies at risk of iodine deficiency? Med J Aust. 2006;184(12): Delange F. Iodine deficiency as a cause of brain damage. Postgrad Med J. 2001;77: Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. [database on the Internet]. WHO Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. [database on the Internet]. WHO WiyadaCharoensiriwatana PS, NoppavanJanejai, et al. Application of geographic information system in TSH neonatal screening for monitoring of iodine deficiency areas in Thailand. The Southeast Asian journal of tropical medicine and public health. 2008;39(2). 7. Herbstman J, Apelberg BJ, Witter FR, Panny S and Goldman LR. Maternal, infant, and delivery factors associated with neonatal thyroid hormone status. Thyroid. 2008;18(1): ภาวะการขาดสารไอโอด น (% IDD) ของทารกแรกเก ด [database on the Internet]. กรมว ทยาศาตร การแพทย กระทรวง สาธารณส ข. Available from:

8 9. ระบบการเฝ าระว งและประเม นผลการป องก นและควบค มภาวะขาดสารไอโอด นในเขต4 [database on the Internet]2547. Available from: WHO/SEARO Meetings: The Fifty-seventh Session of the Regional Committee for South-East Asia. Report of the Fifty-seventh Session, Kurumba, Maldives,7-9 September 2004 [database on the Internet]2004 [cited November 2012]. Available from: Glinoer D 2001 Pregnancy and iodine. Thyroid 11: Boyages SC 1993 Clinical review 49: iodine deficiency disorders. J ClinEndocrinolMetab 77: Marisa Rebagliato MM, Mercedes Espada, and et al. Iodine Intake and Maternal Thyroid Function During Pregnancy. Epidemiology 2010;21: Rajatanavin R. Iodine deficiency in pregnant women and neonates in Thailand. Public Health Nutrition December 2007, pp10(12a):